title: Combinatorial evaluation of in vivo distribution of polyanhydride particle-based platforms for vaccine delivery.
abstract: Several challenges are associated with current vaccine strategies, including repeated immunizations, poor patient compliance, and limited approved routes for delivery, which may hinder induction of protective immunity. Thus, there is a need for new vaccine adjuvants capable of multi-route administration and prolonged antigen release at the site of administration by providing a depot within tissue. In this work, we designed a combinatorial platform to investigate the in vivo distribution, depot effect, and localized persistence of polyanhydride nanoparticles as a function of nanoparticle chemistry and administration route. Our observations indicated that the route of administration differentially affected tissue residence times. All nanoparticles rapidly dispersed when delivered intranasally but provided a depot when administered parenterally. When amphiphilic and hydrophobic nanoparticles were administered intranasally, they persisted within lung tissue. These results provide insights into the chemistry- and route-dependent distribution and tissue-specific association of polyanhydride nanoparticle-based vaccine adjuvants.
authors.affiliation: Department of Chemical and Biological Engineering, Iowa State University, Ames, IA 50011, USA.
authors.forename: Latrisha K
authors.initials: LK
authors.lastname: Petersen
authors.forename: Lucas
authors.initials: L
authors.lastname: Huntimer
authors.forename: Katharine
authors.initials: K
authors.lastname: Walz
authors.forename: Amanda
authors.initials: A
authors.lastname: Ramer-Tait
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Wannemuehler
authors.forename: Balaji
authors.initials: B
authors.lastname: Narasimhan
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D000281:Administration, Intranasal; D000704:Analysis of Variance; D000818:Animals; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D016503:Drug Delivery Systems; D005456:Fluorescent Dyes / Q000737:chemistry; D007273:Injections, Intramuscular; D008168:Lung / Q000737:chemistry; D051379:Mice; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism*; D049388:Polyanhydrides / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D014018:Tissue Distribution; D014612:Vaccines; D051598:Whole Body Imaging
chemical_list: D000276:Adjuvants, Immunologic; D003692:Delayed-Action Preparations; D005456:Fluorescent Dyes; D049388:Polyanhydrides; D014612:Vaccines
keywords: combinatorial; distribution; live animal imaging; nanoparticle; polyanhydride